How genes control development of nerve and muscle is an important and, as yet, unsolved problem in biology and medicine. Such developmental mechanisms are crucially dependent upon the molecular processes that regulate the synthesis and function of specific proteins with respect to cellular location and time of appearance. The elucidation of how these mechanisms operate during embryonic differentiation, larval maturation and adult ageing of the neuromuscular system in nematode worms is the principal objective of this program. The program will focus upon molecular and genetic studies of the body wall muscle cells within these nematodes. The rule of protein components in the assembly and function of the muscle filament lattice will be studied in normal and mutant animals by biochemical, cytochemical, immunological and physical methods. Large numbers of appropriate mutants will be selected on the basis of defective locomotion, abnormal body wall muscle structure and specific differences in electrophoretic mobilities of protein components. Functional and structural characterization of purified proteins from specific mutant strains in correlation with genetic mapping will establish which genetic loci actually code for muscle contractile proteins. Mutants in other genetic elements will be investigated as to whether they code for assembly functions or regulate the synthesis of muscle components. The purification from nematodes of large DNA fragments that contain structural genes for contractile proteins may permit precise dissection of the interrelationship of coding, control and processing that will complement the other approaches. BIBLIOGRAPHIC REFERENCES: Harris, H.E., Tso, M.-Y. and Epstein, H.F. Actin and myosin-linked calcium regulation in the nematode, Caenorhabditis elegans. Biochemistry 16:859-865, 1977. Harris, H.E. and Epstein, H.F. Myosin and paramyosin from Caenorhabditis elegans: Biochemical and structural properties of normal and mutant proteins. Cell 10:709-719, 1977.